Acetic Acid → Tert-butyl (3-((2-((3-(benzyloxy)-4-(2-methoxyethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate

HRID 2274264노트

반응식

HRID 2274264 반응식
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:13]=[CH:14][C:15]=1[O:16][CH2:17][CH2:18][O:19][CH3:20])[NH2:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:22]1[N:27]=[C:26]([NH:28][C:29]2[CH:30]=[C:31]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH:32]=[CH:33][CH:34]=2)[C:25]([F:43])=[CH:24][N:23]=1.CC(O)=O.CCCCCC.C(OCC)(=O)C>C(O)C.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([NH:12][C:22]2[N:27]=[C:26]([NH:28][C:29]3[CH:30]=[C:31]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:39])([CH3:40])[CH3:41])[CH:32]=[CH:33][CH:34]=3)[C:25]([F:43])=[CH:24][N:23]=2)[CH:13]=[CH:14][C:15]=1[O:16][CH2:17][CH2:18][O:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 21226206Ethyl acetate hexaneHCID 59174297Tert-butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)carbamateHCID 867243363-(Benzyloxy)-4-(2-methoxyethoxy)aniline

생성물 1

HCID 86724337Tert-butyl (3-((2-((3-(benzyloxy)-4-(2-methoxyethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate수율 37%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 962Water용매

실험 절차

To a solution of 3-(benzyloxy)-4-(2-methoxyethoxy)aniline (0.500 g) and tert-butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate (0.556 g) in ethanol (10 mL), was added CH3COOH (54 mg). The reaction mixture was heated to reflux for 24 hr. Completion of reaction was monitored by TLC using hexane:ethyl acetate (5:5) as mobile phase. After completion, reaction mixture was allowed to cool at room temperature and poured into cold water. Product was extracted with ethyl acetate (50 mL×3). Ethyl acetate layer washed with 50 mL brine solution. Ethyl acetate layer was dried over sodium sulfate and concentrated under reduced pressure. Crude material was purified by using Combiflash chromatography. Desired spot eluted with 18% ethyl acetate in hexane to give 0.35 g of tert-butyl (3-((2-((3-(benzyloxy)-4-(2-methoxyethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate. 1H NMR: DMSO-d6 (400 MHz): 1.467 (s, 9H), 3.357 (s, 3H), 3.614-3.636 (t, 2H, J=4.4), 4.024-4.046 (t, 2H, J=4.0), 4.921 (s, 2H), 6.811-6.833 (d, 1H, J=8.8), 7.120-7.197 (m, 3H), 7.311-7.448 (m, 7H), 7.827 (s, 1H), 8.05-8.068 (d, 1H, J=3.6), 8.935 (s, 1H), 9.306 (s, 1H), 9.353 (s, 1H).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 24 hr
  3. customCompletion of reaction
  4. customAfter completion, reaction mixture
  5. extractionProduct was extracted with ethyl acetate (50 mL×3)
  6. washEthyl acetate layer washed with 50 mL brine solution
  7. dry with materialEthyl acetate layer was dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customCrude material was purified
  10. washDesired spot eluted with 18% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-d76994645ae14725a5647d59e56498f5
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09126950B2

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